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| | <StructureSection load='3l9j' size='340' side='right'caption='[[3l9j]], [[Resolution|resolution]] 2.10Å' scene=''> | | <StructureSection load='3l9j' size='340' side='right'caption='[[3l9j]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3l9j]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3L9J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3L9J FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3l9j]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3L9J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3L9J FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3l9j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l9j OCA], [http://pdbe.org/3l9j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3l9j RCSB], [http://www.ebi.ac.uk/pdbsum/3l9j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3l9j ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3l9j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l9j OCA], [https://pdbe.org/3l9j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3l9j RCSB], [https://www.ebi.ac.uk/pdbsum/3l9j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3l9j ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[http://www.uniprot.org/uniprot/TNFA_HUMAN TNFA_HUMAN]] Genetic variations in TNF are a cause of susceptibility psoriatic arthritis (PSORAS) [MIM:[http://omim.org/entry/607507 607507]]. PSORAS is an inflammatory, seronegative arthritis associated with psoriasis. It is a heterogeneous disorder ranging from a mild, non-destructive disease to a severe, progressive, erosive arthropathy. Five types of psoriatic arthritis have been defined: asymmetrical oligoarthritis characterized by primary involvement of the small joints of the fingers or toes; asymmetrical arthritis which involves the joints of the extremities; symmetrical polyarthritis characterized by a rheumatoidlike pattern that can involve hands, wrists, ankles, and feet; arthritis mutilans, which is a rare but deforming and destructive condition; arthritis of the sacroiliac joints and spine (psoriatic spondylitis). | |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TNFA_HUMAN TNFA_HUMAN]] Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation.<ref>PMID:16829952</ref> The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.<ref>PMID:16829952</ref> | + | [https://www.uniprot.org/uniprot/TETN_HUMAN TETN_HUMAN] Tetranectin binds to plasminogen and to isolated kringle 4. May be involved in the packaging of molecules destined for exocytosis. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Andersen, M H]] | + | [[Category: Andersen MH]] |
| - | [[Category: Byla, P]] | + | [[Category: Byla P]] |
| - | [[Category: Gad, H H]] | + | [[Category: Gad HH]] |
| - | [[Category: Hartmann, R]] | + | [[Category: Hartmann R]] |
| - | [[Category: Thogersen, H C]] | + | [[Category: Thogersen HC]] |
| - | [[Category: Antagonist]]
| + | |
| - | [[Category: Cell membrane]]
| + | |
| - | [[Category: Cytokine]]
| + | |
| - | [[Category: Disulfide bond]]
| + | |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: In vitro selection]]
| + | |
| - | [[Category: Lipoprotein]]
| + | |
| - | [[Category: Secreted]]
| + | |
| - | [[Category: Signal-anchor]]
| + | |
| - | [[Category: Tnf-alpha]]
| + | |
| - | [[Category: Transmembrane]]
| + | |
| Structural highlights
Function
TETN_HUMAN Tetranectin binds to plasminogen and to isolated kringle 4. May be involved in the packaging of molecules destined for exocytosis.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Inhibition of tumor necrosis factor alpha (TNFalpha) is a favorable way of treating several important diseases such as rheumatoid arthritis, Crohn disease, and psoriasis. Therefore, an extensive range of TNFalpha inhibitory proteins, most of them based upon an antibody scaffold, has been developed and used with variable success as therapeutics. We have developed a novel technology platform using C-type lectins as a vehicle for the creation of novel trimeric therapeutic proteins with increased avidity and unique properties as compared with current protein therapeutics. We chose human TNFalpha as a test target to validate this new technology because of the extensive experience available with protein-based TNFalpha antagonists. Here, we present a novel and highly specific TNFalpha antagonist developed using this technology. Furthermore, we have solved the three-dimensional structure of the antagonist-TNFalpha complex by x-ray crystallography, and this structure is presented here. The structure has given us a unique insight into how the selection procedure works at a molecular level. Surprisingly little change is observed in the C-type lectin-like domain structure outside of the randomized regions, whereas a substantial change is observed within the randomized loops. Thus, the overall integrity of the C-type lectin-like domain is maintained, whereas specificity and binding affinity are changed by the introduction of a number of specific contacts with TNFalpha.
Selection of a novel and highly specific tumor necrosis factor alpha (TNFalpha) antagonist: insight from the crystal structure of the antagonist-TNFalpha complex.,Byla P, Andersen MH, Holtet TL, Jacobsen H, Munch M, Gad HH, Thogersen HC, Hartmann R J Biol Chem. 2010 Apr 16;285(16):12096-100. Epub 2010 Feb 23. PMID:20179326[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Byla P, Andersen MH, Holtet TL, Jacobsen H, Munch M, Gad HH, Thogersen HC, Hartmann R. Selection of a novel and highly specific tumor necrosis factor alpha (TNFalpha) antagonist: insight from the crystal structure of the antagonist-TNFalpha complex. J Biol Chem. 2010 Apr 16;285(16):12096-100. Epub 2010 Feb 23. PMID:20179326 doi:10.1074/jbc.M109.063305
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